Six3 demarcates the anterior-most developing brain region in bilaterian animals. EvoDevo 1:14

University of Vienna, Department for Molecular Evolution and Development, Althanstrasse 14, A-1090 Vienna, Austria.
EvoDevo (Impact Factor: 3.03). 12/2010; 1(1):14. DOI: 10.1186/2041-9139-1-14
Source: PubMed


The heads of annelids (earthworms, polychaetes, and others) and arthropods (insects, myriapods, spiders, and others) and the arthropod-related onychophorans (velvet worms) show similar brain architecture and for this reason have long been considered homologous. However, this view is challenged by the 'new phylogeny' placing arthropods and annelids into distinct superphyla, Ecdysozoa and Lophotrochozoa, together with many other phyla lacking elaborate heads or brains. To compare the organisation of annelid and arthropod heads and brains at the molecular level, we investigated head regionalisation genes in various groups. Regionalisation genes subdivide developing animals into molecular regions and can be used to align head regions between remote animal phyla.
We find that in the marine annelid Platynereis dumerilii, expression of the homeobox gene six3 defines the apical region of the larval body, peripherally overlapping the equatorial otx+ expression. The six3+ and otx+ regions thus define the developing head in anterior-to-posterior sequence. In another annelid, the earthworm Pristina, as well as in the onychophoran Euperipatoides, the centipede Strigamia and the insects Tribolium and Drosophila, a six3/optix+ region likewise demarcates the tip of the developing animal, followed by a more posterior otx/otd+ region. Identification of six3+ head neuroectoderm in Drosophila reveals that this region gives rise to median neurosecretory brain parts, as is also the case in annelids. In insects, onychophorans and Platynereis, the otx+ region instead harbours the eye anlagen, which thus occupy a more posterior position.
These observations indicate that the annelid, onychophoran and arthropod head develops from a conserved anterior-posterior sequence of six3+ and otx+ regions. The six3+ anterior pole of the arthropod head and brain accordingly lies in an anterior-median embryonic region and, in consequence, the optic lobes do not represent the tip of the neuraxis. These results support the hypothesis that the last common ancestor of annelids and arthropods already possessed neurosecretory centres in the most anterior region of the brain. In light of its broad evolutionary conservation in protostomes and, as previously shown, in deuterostomes, the six3-otx head patterning system may be universal to bilaterian animals.

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    • "Another example of a miRNA target of the homeobox transcription factor family in Nematostella is NvSix3/6. Six3/6 specifies the anterior-most part of the bilaterian brain and epidermis and has a role as an upstream regulator of the apical domain in the larva of Nematostella (Steinmetz et al. 2010; Sinigaglia et al. 2013). The Nematostella Six3/6 binding site for miR-2025 in the coding sequence (CDS) is conserved in the orthologous transcripts from the anemone species Anemonia viridis and Anthopleura japonica, despite poor overall sequence conservation of the mRNAs (Fig. 5C). "
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    ABSTRACT: In bilaterians, which comprise most of extant animals, microRNAs (miRNAs) regulate the majority of messenger RNAs (mRNAs) via base-pairing of a short sequence (the miRNA "seed") to the target, subsequently promoting translational inhibition and transcript instability. In plants, many miRNAs guide endonucleolytic cleavage of highly complementary targets. Because little is known about miRNA function in nonbilaterian animals, we investigated the repertoire and biological activity of miRNAs in the sea anemone Nematostella vectensis, a representative of Cnidaria, the sister phylum of Bilateria. Our work uncovers scores of novel miRNAs in Nematostella, increasing the total miRNA gene count to 87. Yet only a handful are conserved in corals and hydras, suggesting that microRNA gene turnover in Cnidaria greatly exceeds that of other metazoan groups. We further show that Nematostella miRNAs frequently direct the cleavage of their mRNA targets via nearly perfect complementarity. This mode of action resembles that of small interfering RNAs (siRNAs) and plant miRNAs. It appears to be common in Cnidaria, as several of the miRNA target sites are conserved among distantly related anemone species, and we also detected miRNA-directed cleavage in Hydra. Unlike in bilaterians, Nematostella miRNAs are commonly coexpressed with their target transcripts. In light of these findings, we propose that post-transcriptional regulation by miRNAs functions differently in Cnidaria and Bilateria. The similar, siRNA-like mode of action of miRNAs in Cnidaria and plants suggests that this may be an ancestral state.
    Full-text · Article · Mar 2014 · Genome Research
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    • "Likewise, fezf is expressed in the apical plate in sea urchin [32] and the hemichordate [33]. We have previously shown that six3 is expressed in a large contiguous domain of the Platynereis episphere [34], peripherally overlapping with the expression of rx[35]. "
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    ABSTRACT: Planktonic ciliated larvae are characteristic for the life-cycle of marine invertebrates. Their most prominent feature is the apical organ harbouring sensory cells and neurons of largely undetermined function. An elucidation of the relationships between various forms of primary larvae and apical organs is key to understanding the evolution of animal life-cycles. These relationships have remained enigmatic due to the scarcity of comparative molecular data. To compare apical organs and larval body patterning, we have studied regionalization of the episphere, the upper hemisphere of the trochophore larva of the marine annelid Platynereis dumerilii. We examine the spatial distribution of transcription factors and of Wnt signalling components previously implicated in anterior neural development. Pharmacological activation of Wnt signaling with Gsk3beta antagonists abolishes expression of apical markers, consistent with a repressive role of Wnt signalling in the specification of apical tissue. We refer to this Wnt-sensitive, six3- and foxq2-expressing part of the episphere as 'apical plate'. We also unravel a molecular signature of the apical organ - devoid of six3 but expressing foxj, irx, nkx3 and hox - which is shared with other marine phyla including cnidarians. Finally, we characterize the cell types that form part of the apical organ by PrImR (Profiling by Image Registration), which allows parallel expression profiling of multiple cells. Besides the hox-expressing apical tuft cells this reveals the presence of putative light- and mechanosensory as well as multiple peptidergic cell types that we compare to apical organ cell types of other animal phyla. The similar formation of a six3+, foxq2+ apical plate, sensitive to wnt activity and with an apical tuft in its six3-free centre, are most parsimoniously explained by evolutionary conservation. We propose that a simple apical organ - comprising an apical tuft and a basal plexus innervated by sensory-neurosecretory apical plate cells - was present in the last common ancestors of cnidarians and bilaterians. One of its ancient functions was the control of metamorphosis. Various types of apical plate cells were subsequently added to the apical organ in the divergent bilaterian lineages. Our findings support an ancient and common origin of primary ciliated larvae.
    Full-text · Article · Jan 2014 · BMC Biology
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    • "PC, protocerebrum; DC, deutocerebrum; TC, tritocerebrum; VC, ventral nerve cord; CG, cerebral ganglion; SG, segmental ganglia; FB, forebrain; MB, midbrain; HB, hindbrain; SC, spinal cord. Gene expression domains based on [1,2,9,24,29,34,42,64],[68-80]. "
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    ABSTRACT: The question of whether the ancestral bilaterian had a central nervous system (CNS) or a diffuse ectodermal nervous system has been hotly debated. Considerable evidence supports the theory that a CNS evolved just once. However, an alternative view proposes that the chordate CNS evolved from the ectodermal nerve net of a hemichordate-like ancestral deuterostome, implying independent evolution of the CNS in chordates and protostomes. To specify morphological divisions along the anterior/posterior axis, this ancestor used gene networks homologous to those patterning three organizing centers in the vertebrate brain: the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer, and subsequent evolution of the vertebrate brain involved elaboration of these ancestral signaling centers; however, all or part of these signaling centers were lost from the CNS of invertebrate chordates. The present review analyzes the evidence for and against these theories. The bulk of the evidence indicates that a CNS evolved just once -- in the ancestral bilaterian. Importantly, in both protostomes and deuterostomes, the CNS represents a portion of a generally neurogenic ectoderm that is internalized and receives and integrates inputs from sensory cells in the remainder of the ectoderm. The expression patterns of genes involved in medio/lateral (dorso/ventral) patterning of the CNS are similar in protostomes and chordates; however, these genes are not similarly expressed in the ectoderm outside the CNS. Thus, their expression is a better criterion for CNS homologs than the expression of anterior/posterior patterning genes, many of which (for example, Hox genes) are similarly expressed both in the CNS and in the remainder of the ectoderm in many bilaterians. The evidence leaves hemichordates in an ambiguous position -- either CNS centralization was lost to some extent at the base of the hemichordates, or even earlier, at the base of the hemichordates + echinoderms, or one of the two hemichordate nerve cords is homologous to the CNS of protostomes and chordates. In any event, the presence of part of the genetic machinery for the anterior neural ridge, the zona limitans intrathalamica and the isthmic organizer in invertebrate chordates together with similar morphology indicates that these organizers were present, at least in part, at the base of the chordates and were probably elaborated upon in the vertebrate lineage.
    Full-text · Article · Oct 2013 · EvoDevo
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